Bone Marrow Mesenchymal Stromal Cells Rescue Cardiac Function in Streptozotocin-Induced Diabetic Rats.

OBJECTIVES:In the present study, we investigated whether MSC-transplantation can revert cardiac dysfunction in streptozotocin-induced diabetic rats and the immunoregulatory effects of MSC were examined.BACKGROUND:Cardiac complications are one of the main causes of death in diabetes. Several studies have shown anti-diabetic effects of bone marrow mesenchymal stromal cells (MSC).METHODS/RESULTS:The rats were divided in three groups: Non-diabetic, Diabetic and Diabetic-Treated with 5 × 10(6) MSC 4 weeks after establishment of diabetes. Four weeks after MSC-therapy, systemic metabolic parameters, immunological profile and cardiac function were assessed. MSC-transplantation was able to revert the hyperglycemia and body weight loss of the animals. In addition, after MSC-transplantation a decrease in corticosterone and IFN-γ sera levels without restoration of insulin and leptin plasma levels was observed. Also, MSC-therapy improved electrical remodeling, shortening QT and QTc in the ECG and action potential duration of left ventricular myocytes. No arrhythmic events were observed after MSC-transplantation. MSC-therapy rescued the cardiac beta-adrenergic sensitivity by increasing beta-1 adrenergic receptor expression. Both alpha and beta cardiac AMPK and p-AMPK returned to baseline values after MSC-therapy. However, total ERK1 and p-ERK1/2 were not different among groups.CONCLUSION:The results indicate that MSC-therapy was able to rescue cardiac impairment induced by diabetes, normalize cardiac AMPK subunit expression and activity, decrease corticosterone and glycemia and exert systemic immunoregulation.